tbuckley/cabot-search huggingface dataset:
Prepregnancy body mass index and risk of childhood asthma
Authors: Natalie A. Rosenquist, Megan Richards, Jeannette R. Ferber, De‐Kun Li, So Young Ryu, Heather Burkin, Matthew J. Strickland, Lyndsey A. Darrow
Journal: Allergy (2022)

Abstract Background Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child's risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk. Methods Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005–2014) to age 4 ( n = 104,467), 6 ( n = 63,084), or 8 ( n = 31,006) using electronic medical records. Child's asthma was defined using ICD codes and asthma‐related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child's asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [&lt;18.5], normal [18.5–24.9], overweight [25–29.9], obese 1 [30–34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI. Results Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI. Conclusions Higher prepregnancy BMI is associated with modestly increased childhood asthma risk.
Secondary hemophagocytic lymphohistiocytosis following Zolgensma therapy: An evolving story on the innate response to systemic gene therapy
Authors: Barry J. Byrne, Melissa Elder, Carmen Leon-Astudillo, Manuela Corti
Journal: Molecular Therapy (2022)

Treatment of spinal muscular atrophy (SMA) has been transformed since the development of targeted therapies such as nusinersen, 1 Hoy S.M. Nusinersen: first global approval. Drugs. 2017; 77: 473-479https://doi.org/10.1007/s40265-017-0711-7 Crossref PubMed Scopus (163) Google Scholar risdiplam, 2 Dhillon S. Risdiplam: first approval. Drugs. 2020; 80: 1853-1858https://doi.org/10.1007/s40265-020-01410-z Crossref PubMed Scopus (84) Google Scholar and onasemogene abeparvovec-xioi (Zolgensma). 3 Hoy S.M. Onasemnogene abeparvovec: first global approval. Drugs. 2019; 79: 1255-1262https://doi.org/10.1007/s40265-019-01162-5 Crossref PubMed Scopus (180) Google Scholar The disease-modifying impact of gene therapy for SMA and the advent of newborn screening accompanied by early treatment have made single-dose therapy a preferred choice for parents and providers. It has been difficult to differentiate the severe nature of the underlying condition and safety events following Zolgensma, which have been attributed to the therapy. Ascertainment of safety events is further complicated by the lack of a Risk Evaluation and Mitigation Strategy (REMS) program for the drug. Therefore, individual providers who have identified safety events must take the initiative to report those findings in the literature, 4 Guillou J. de Pellegars A. Porcheret F. Frémeaux-Bacchi V. Allain-Launay E. Debord C. Denis M. Péréon Y. Barnérias C. Desguerre I. et al. Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy. Blood Adv. 2022; 6: 4266-4270https://doi.org/10.1182/bloodadvances.2021006419 Crossref PubMed Scopus (28) Google Scholar or they must be reported by sponsor-driven post-marketing findings. 5 Day J.W. Mendell J.R. Mercuri E. Finkel R.S. Strauss K.A. Kleyn A. Tauscher-Wisniewski S. Tukov F.F. Reyna S.P. Chand D.H. Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy. Drug Saf. 2021; 44: 1109-1119https://doi.org/10.1007/s40264-021-01107-6 Crossref PubMed Scopus (41) Google Scholar In a recent report by Galletta et al., 6 Galletta F. Cucinotta U. Marseglia L. Cacciola A. Gallizzi R. Cuzzocrea S. Messina S. Toscano A. Gitto E. Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy. J. Clin. Pharm. Ther. 2022; 47: 1478-1481https://doi.org/10.1111/jcpt.13733 Crossref PubMed Scopus (6) Google Scholar the authors describe a case of acquired hemophagocytic lymphohistiocytosis (HLH) that occurred in a patient with SMA who was treated with Zolgensma in Italy. The observations in this case report expand on the findings of immune response to systemic administration of adeno-associated virus (AAV) vectors and provide insight into adverse events in humans that have been difficult to model in non-clinical studies.
siRNA delivery to lymphatic endothelial cells via ApoE-mediated uptake by lipid nanoparticles
Authors: Yu Sakurai, Keito Yoshikawa, Kenta Arai, Akira Kazaoka, Shigeki Aoki, Kousei Ito, Yuta Nakai, Kota Tange, Tomomi Furihata, Hiroki Tanaka, Hidetaka Akita
Journal: Journal of Controlled Release (2022)
Polymer- and lipid-based gene delivery technology for CAR T cell therapy
Authors: Inês S. Pinto, Rosemeyre A. Cordeiro, Henrique Faneca
Journal: Journal of Controlled Release (2022)

Chimeric antigen receptor T cell (CAR T cell) therapy is a revolutionary approach approved by the FDA and EMA to treat B cell malignancies and multiple myeloma. The production of these T cells has been done through viral vectors, which come with safety concerns, high cost and production challenges, and more recently also through electroporation, which can be extremely cytotoxic. In this context, nanosystems can constitute an alternative to overcome the challenges associated with current methods, resulting in a safe and cost-effective platform. However, the barriers associated with T cells transfection show that the design and engineering of novel approaches in this field are highly imperative. Here, we present an overview from CAR constitution to transfection technologies used in T cells, highlighting the lipid- and polymer-based nanoparticles as a potential delivery platform. Specifically, we provide examples, strengths and weaknesses of nanosystem formulations, and advances in nanoparticle design to improve transfection of T cells. This review will guide the researchers in the design and development of novel nanosystems for next-generation CAR T therapeutics.
Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies
Authors: Kim Papp, Jacek C. Szepietowski, Leon Kircik, Darryl Toth, Lawrence F. Eichenfield, Seth B. Forman, Michael E. Kuligowski, Howard Kallender, Kang Sun, Haobo Ren, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2022)
Serological response to COVID-19 vaccine and its predictors in patients with solid malignancies: A systematic review and meta-analysis of 16 cohort studies
Authors: Dong Chen, Yuancan Pan, Yue Wang, Xing Chen, Jiahui Zhang, Yutong Zhang, Tongjing Ding, Zhengzheng Yang, Taicheng Lu, Yingying Zheng, Jiangyan Wei, Weijia Kong, Haiming Li, Xiaohui Yin, Guowang Yang, Ganlin Zhang, Xiaomin Wang
Journal: Journal of Infection (2022)
Re: Juan Gómez Rivas, Bhaskar Somani, Moises Rodriguez Socarrás, et al. Shaping the Undergraduate Curriculum in Europe: Consensus Statement from the European School of Urology. Eur Urol. 2022;82:581–83
Authors: Alexander Ng, Aqua Asif, Veeru Kasivisvanathan
Journal: European Urology (2022)
Water-responsive 4D printing based on self-assembly of hydrophobic protein “Zein” for the control of degradation rate and drug release
Authors: Yubei Zhang, Ali Raza, Ya-Qi Xue, Ganggang Yang, Uzma Hayat, Jingwen Yu, Chang Liu, Hua-Jie Wang, Jin-Ye Wang
Journal: Bioactive Materials (2022)

Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.
Matrix from urine stem cells boosts tissue-specific stem cell mediated functional cartilage reconstruction
Authors: Ming Pei, Yixuan Amy Pei, Sheng Zhou, Elmira Mikaeiliagah, Christopher Erickson, Benjamin Giertych, Halima Akhter, Lei Wang, Amanda Stewart, Joshua Parenti, Bin Wang, Sijin Wen, Sotcheadt Sim, Eric Quenneville, Kirk C. Hansen, Steven Frisch, Gangqing Hu
Journal: Bioactive Materials (2022)

Articular cartilage has a limited capacity to self-heal once damaged. Tissue-specific stem cells are a solution for cartilage regeneration; however, ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration. Our previous report demonstrated that decellularized extracellular matrix (dECM) deposited by human synovium-derived stem cells (SDSCs), adipose-derived stem cells (ADSCs), urine-derived stem cells (UDSCs), or dermal fibroblasts (DFs) provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential, particularly for dECM deposited by UDSCs. To make the cell-derived dECM (C-dECM) approach applicable clinically, in this study, we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells (IPFSCs), an easily accessible alternative for SDSCs, by the abovementioned C-dECMs, in vivo application for functional cartilage repair in a rabbit osteochondral defect model, and potential cellular and molecular mechanisms underlying this rejuvenation. We found that C-dECM rejuvenation promoted rabbit IPFSCs' cartilage engineering and functional regeneration in both ex vivo and in vivo models, particularly for the dECM deposited by UDSCs, which was further confirmed by proteomics data. RNA-Seq analysis indicated that both mesenchymal-epithelial transition (MET) and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs' chondrogenic capacity, which needs further investigation.
Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment
Authors: Reihaneh Haghniaz, Han-Jun Kim, Hossein Montazerian, Avijit Baidya, Maryam Tavafoghi, Yi Chen, Yangzhi Zhu, Solmaz Karamikamkar, Amir Sheikhi, Ali Khademhosseini
Journal: Bioactive Materials (2022)

Blood loss by hemorrhaging wounds accounts for over one-third of ∼5 million trauma fatalities worldwide every year. If not controlled in a timely manner, exsanguination can take lives within a few minutes. Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need. Here, biocompatible, and biodegradable microneedle arrays (MNAs) based on gelatin methacryloyl (GelMA) biomaterial hybridized with silicate nanoplatelets (SNs) are developed for hemorrhage control. The SNs render the MNAs hemostatic, while the needle-shaped structure increases the contact area with blood, synergistically accelerating the clotting time from 11.5 min to 1.3 min
Photothermal Enhanced and Tumor Microenvironment Responsive Nanozyme for Amplified Cascade Enzyme Catalytic Therapy
Authors: Yang Zhu, Yuanbo Pan, Zhengxi Guo, Duo Jin, Wenyu Wang, Manman Liu, Mingxi Zong, Xinwei Zheng, Yun Wu, Lulu Wang, Changlin Tian, Junjie Cheng, Yangzhong Liu
Journal: Advanced Healthcare Materials (2022)

Nanocatalysts, a class of nanomaterials with intrinsic enzyme-like activities, have been widely investigated for cancer catalytic therapy in recent years. However, precise construction of nanocatalysts with excellent enzyme catalytic activity and biosafety for tumor therapy still remains challenging. Here, a biodegradable nanocatalyst, PEGylated Cux Mny Sz (PCMS), is reported that can promote cascade catalytic reactions in tumor microenvironment (TME) while confining off-target side effects on normal tissues. PCMS not only catalyzes the cascade conversion of endogenous hydrogen peroxide (H2 O2 ) to oxygen (O2 ) via catalase-like activity and then to superoxide radical (·O2- ) via oxidase-like activity in the TME, but also effectively depletes intracellular glutathione via glutathione oxidase-like activity. The cascade catalytic reactions, by taking advantage of high H2 O2 level in tumor cells, result in an enhanced enzyme catalytic effect in generation of ·O2- . More importantly, PCMS exhibits prominent photothermal effect under NIR-II 1064 nm laser irradiation that can further enhance chemodynamic therapy (CDT) efficacy in tumors. In addition, the biodegradation in TME and excellent photothermal effect of PCMS are beneficial to magnetic resonance imaging, photoacoustic imaging and infrared thermal imaging, resulting in tracing the fate of PCMS in vivo. This study provides a new tool for rational design of TME-responsive nanocatalysts with high biocompatibility for tumor catalytic therapy.
Nanodroplet‐Coated Microbubbles Used in Sonothrombolysis with Two‐Step Cavitation Strategy
Authors: Yunfan Pan, Yongjian Li, Yan Li, Xiaobing Zheng, Chenghong Zou, Jiang Li, Haosheng Chen
Journal: Advanced Healthcare Materials (2022)

Abstract Thrombosis is a major cause of morbidity and mortality and sonothrombolysis is a promising method for its treatment. However, the slow diffusion of the thrombolytic agents into the thrombus results in slow recanalization. Here, nanodroplet‐coated microbubbles (NCMBs) are designed and fabricated and a two‐step cavitation strategy is used to accelerate the thrombolysis. The first cavitation of the NCMBs, cavitation and collapse of the microbubbles induced by low frequency ultrasound, drives the nanodroplets on the shell into the thrombus, while the second cavitation, the phase‐change and volume expansion of drug‐loaded nanodroplets triggered by high frequency ultrasound, loosens the thrombus by the sono‐porosity effect. This two‐step cavitation of the NCMBs is verified using a fibrin agarose model, where a rapid diffusion of the thrombolytic agents is observed. Furthermore, the NCMBs reach much higher thrombolysis efficiency in both in vitro and proof‐of‐concept experiments performed with living mice. The nanodroplet‐coated microbubbles are a promising diffusion medicines carrier for efficient drug delivery.
Advances in diagnosis and treatment of testicular cancer
Authors: Michal Chovanec, Liang Cheng
Journal: BMJ (2022)

Abstract Testicular cancer is a curable cancer. The success of physicians in curing the disease is underpinned by multidisciplinary advances. Cisplatin-based combination chemotherapy and the refinement of post-chemotherapy surgical procedures and diagnostic strategies have greatly improved long term survival in most patients. Despite such excellent outcomes, several controversial dilemmas exist in the approaches to clinical stage I disease, salvage chemotherapy, post-chemotherapy surgical procedures, and implementing innovative imaging studies. Relapse after salvage chemotherapy has a poor prognosis and the optimal treatment is not apparent. Recent research has provided insight into the molecular mechanisms underlying cisplatin resistance. Phase 2 studies with targeted agents have failed to show adequate efficacy; however, our understanding of cisplatin resistant disease is rapidly expanding. This review summarizes recent advances and discusses relevant issues in the biology and management of testicular cancer.
Author's correction for Euro Surveill. 2022;27(46)
Journal: Eurosurveillance (2022)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022
Rotavirus epidemiology and genotype distribution in hospitalised children, Greece, 2008 to 2020: A prospective multicentre study
Authors: Dimitra-Maria Koukou, Athanasios Michos, Panagiota Chatzichristou, Georgios Trimis, Elizabeth-Barbara Tatsi, Charilaos Dellis, Levantia Zachariadou, Theodota Liakopoulou, George P Chrousos, Vasiliki Syriopoulou
Journal: Eurosurveillance (2022)

Background Two rotavirus (RV) vaccines were licensed in Greece in late 2006 and included in the national immunisation programme in 2012. Aim To study the epidemiology and genotype distribution of RV in children during the post-vaccination period and assess the impact of increased vaccination coverage. Methods In a prospective multicentre hospital-based study, hospitalised children (≤ 16 years) with an RV-positive faecal sample were recruited. Epidemiological and genotyping analyses were performed; periods of low (2008–12) and moderate (2012–20) RV vaccination coverage were compared. Statistical analysis was performed with a chi-squared or Mann–Whitney U test and logistic regression. Results A total of 3,874 children (55.6% male; n = 2,153) with median age of 1.4 years (IQR: 0.5–3.3) were studied during 2008–20. Most RV-infected children were aged ≤ 3 years (72.2%) and hospitalised during December–May (69.1%). Common RV genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], G12P[8]) were detected in 92.2% of samples; G-P combinations with prevalence above 1% were G4P[8] (44.1%), G1P[8] (25.4%), G2P[4] (14.9%), G9P[8] (3.5%), G12P[8] (2.2%), G3P[8] (2.1%), other (4.3%) and mixed (3.5%). Of all samples, 97.6% were homotypic or partially heterotypic to vaccines’ genotypes. With moderate vaccination coverage, the seasonal peak was detected earlier, children were older and partially or fully heterotypic genotypes were increased (p &lt; 0.001). Conclusions In the era of moderate RV vaccination coverage in Greece, epidemiology of RV in hospitalised children seemed to change. However, most circulating genotypes remain homotypic or partially heterotypic to RV vaccines. Continuous epidemiological surveillance and genotyping are important to monitor possible changes arising from RV vaccines’ implementation.
Transform-Us! cluster RCT: 18-month and 30-month effects on children’s physical activity, sedentary time and cardiometabolic risk markers
Authors: Jo Salmon, Lauren Arundell, Ester Cerin, Nicola Dawn Ridgers, Kylie D Hesketh, Robin M Daly, David Dunstan, Helen Brown, Jacqui Della Gatta, Paul Della Gatta, Mai J M Chinapaw, Lauren Shepphard, Marj Moodie, Clare Hume, Vicki Brown, Kylie Ball, David Crawford
Journal: British Journal of Sports Medicine (2022)

Objective To test the efficacy of the Transform-Us! school- and home-based intervention on children’s physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles. Methods A 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010–2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed. Results At 18 months, there were intervention effects on children’s weekday SB (−27 min, 95% CI: −47.3 to −5.3) for the PA intervention, and on children’s average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children’s average day SB (−33.3 min, 95% CI: −50.6 and −16.0) for the SB intervention. Children’s BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters. Conclusions The Transform-Us! PA and SB interventions show promise as a pragmatic approach for reducing children’s SB and adiposity indicators; but achieving substantial increases in PA remains challenging. Trial registration ISRCTN83725066 ; ACTRN12609000715279.
A central role for STAT5 in the transcriptional programing of T helper cell metabolism
Authors: Alejandro V. Villarino, Arian DJ Laurence, Fred P. Davis, Luis Nivelo, Stephen R. Brooks, Hong-Wei Sun, Kan Jiang, Behdad Afzali, Daniela Frasca, Lothar Hennighausen, Yuka Kanno, John J. O’Shea
Journal: Science Immunology (2022)

Activated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (cγ) family cytokines are central to these processes, but the role of downstream signal transducer and activator of transcription 5 (STAT5) signaling, which is engaged by all cγ members, is poorly understood. Using genome-, transcriptome-, and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4 + T helper cells. Mechanistically, STAT5 localizes to an array of enhancers and promoters for genes encoding essential enzymes and transporters, where it facilitates p300 recruitment and epigenetic remodeling. We also find that STAT5 licenses the activity of two other key metabolic regulators, the mTOR signaling pathway and the MYC transcription factor. Building on the latter, we present evidence for transcriptome-wide cooperation between STAT5 and MYC in both normal and transformed T cells. Together, our data provide a molecular framework for transcriptional programing of T cell metabolism downstream of cγ cytokines and highlight the JAK-STAT pathway in mediating cellular growth and proliferation.